The objectives of this study are to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and clinical outcome of patients who have severe pneumonia caused by Staphylococcus aureus (S. aureus) after a single intravenous administration of KBSA301 in addition of standard of care antibiotic treatment.

Incidence of adverse events [ Time Frame: From drug administration up to 107 days ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Area Under the Curve (AUC) in plasma of KBSA301 after a single-dose intravenous administration [ Time Frame: Predose and 1, 2, 4, 12, 24, 48 hours after start of infusion, and on Days 8, 15, 29, 57, 85, and 107 post dose ] [ Designated as safety issue: No ]

KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.

Other Name: AR301

Experimental: KBSA301, a monoclonal antibody dose 2

3 mg/kg KBSA301

Drug: KBSA301

KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.

Other Name: AR301

Experimental: KBSA301, a monoclonal antibody dose 3

10 mg/kg KBSA301

Drug: KBSA301

KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.

Other Name: AR301

Experimental: KBSA301, a monoclonal antibody dose 4

20 mg/kg KBSA301

Drug: KBSA301

KBSA301 administered as a single intravenous infusion at dose 1, 2, 3 and 4.

Other Name: AR301

Experimental: Placebo

KBSA301-placebo

Drug: Placebo

Placebo administered as a single intravenous infusion

Other Name: Placebo KBSA301

Detailed Description:

S. aureus is a leading cause of bloodstream, skin, soft tissue, and lower respiratory tract infections worldwide. The frequencies of both nosocomial and community-acquired S. aureus infections have increased steadily over the years and the treatment of these infections has become more challenging due to the emergence of multi-drug resistant strains (e.g. methicillin-resistant Staphylococcus aureus).

S. aureus has several virulence factors that contribute to the pathogenesis of the infection. Amongst them, alpha-toxin that is involved in the pathogenesis of pneumonia, as it leads to apoptosis and cell lysis, in particular lymphocytes, macrophages, alveolar epithelial cells, pulmonary endothelium, and thrombocytes.

In spite of preventive measures for S. aureus infections and current medical treatment (mostly antibiotic therapy, alone or in combination), there is a clear unmet medical need in the clinic for additional treatment options. Passive immunotherapy with monoclonal antibodies may improve treatment options for severe and life-threatening infections like those caused by S. aureus.

Written informed consent provided by the patient, the relatives or the designated trusted person and/or according to local guidelines

Exclusion Criteria:

Women of child bearing potential are excluded from the participation from the study unless they have a negative pregnancy test at baseline and during the course of the study. Postmenopausal women or females that have been surgically sterilized are allowed to participate.

Hypersensitivity to excipients or to any prescribed medication

Severe neutropenia, lymphoma or anticipated chemotherapy

Patients who have long-term tracheostomy

Current or recent investigational drug (within 30 days of enrollment, or 5 half-lives of the investigational compound, whichever is longer)

Known bronchial obstruction or a history of post-obstructive pneumonia.

Active primary lung cancer or another malignancy metastatic to the lungs

Cystic fibrosis, known or suspected Pneumocystis jiroveci pneumonia, or known or suspected active tuberculosis

Immunosuppressive therapy

Liver function deficiency

Moribund clinical condition

Contacts and Locations

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For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01589185